Embodiments of the present invention relate generally to methods and systems for biological and chemical analysis, and more specifically to fluidic methods and systems for preparing and using microarrays in biological and chemical analysis.
Microarrays may be used in various types of biological and chemical analysis, such as in genomic research, drug screening, or screening for infectious diseases. Microarrays generally include sample regions of known biomolecules, also referred to as probes, that are immobilized onto a surface of a substrate, such as a slide. The probes may be, for example, polynucleotides, proteins, other chemical compounds, or tissues. The sample regions are arranged on the surface (e.g., rows and columns) so that each sample region will have a known location or address on the surface of the substrate. The sample regions are then exposed to a target solution containing biomolecules, also called targets, to determine if the targets bind to any of the probes.
For example, in one conventional system, the sample regions are located in an array at the bottom of a well in a microplate. A loading station that has several pipettes or syringes is used to deliver a drop of a target solution into each of the wells so that the drop is placed onto the corresponding sample region. The biomolecules of the target solution are labeled so that the target biomolecules have an optically detectable quality (e.g, fluorescence). When exposed to the probes of the sample regions, the target biomolecules selectively bind (e.g., through hybridization) with certain probes. To facilitate the binding process, the microarray may be placed within an oven where the microarray undergoes a predetermined thermal cycle. After the binding reaction is completed, the microarray is washed to remove any undesired residue and may be then exposed to other solutions (e.g., another target solution, staining solutions). When ready, the microarray is scanned to determine which probes have a binding affinity for the target biomolecules. For example, if the target biomolecules were fluorescently labeled, a reader could scan the microarray to detect any fluorescence. The level of fluorescence emitting from each sample region (or from particular portions of each sample region) indicates a binding affinity that the probes and target biomolecules have for each other. The observed fluorescent pattern provides information on the sequence or structure of the target biomolecules.
However, the process for providing a solution to the sample regions may have certain limitations. For example, when the drop of the target solution is placed onto the corresponding sample region, small bubbles may form within the drop on the surface of the substrate. If the bubbles are located on the sample region, the bubbles may prevent the biomolecules of the target solution from interacting with the probes of the sample region. When the sample region is subsequently scanned, those portions of the sample region where the bubbles prevented the interaction between the biomolecules and probes may not indicate the correct binding affinity. Some methods have been used for removing the bubbles from the target solution when the target solution has been deposited onto the sample region. For example, each well of the microplate may include a separate outlet or channel for removing gases or bubbles formed within the solution. However, using a separate channel to remove the bubbles adds complexity to the system and may also reduce the available space on the microarray.
Another limitation is that conventional loading stations typically use automated or robotic devices for delivering the target solution onto the sample regions. The loading stations are programmed to draw solution from a source or reservoir (e.g., with pipettes or syringes) and automatically deliver the solution to the wells of the microplate. However, the conventional loading stations are complex systems that may be very expensive and require maintenance that is also costly. Furthermore, the loading stations may be limited in the types of microarrays (e.g., size and density of sample regions) that are compatible with the loading stations.
Accordingly, there is a need for improved systems, devices, and methods for reducing gases within a solution. There is also a need for improved systems, devices, and methods for conveying the target solution to the sample region in an efficient manner. Furthermore, there is a need for improved methods and systems for fluidic control during biological or chemical assays.